Yin Qing-Hua, Zhou Qiang, Hu Jian-Bing, Weng Jie, Shen Er-Dong, Wen Fang, Liu Song-Lian, Yin Lei-Lan, Tong Ya-Jun, Long Ling, Tang Ke-Wei, Bai Si-Te, Ou Lu-Di
Department of Oncology, Yueyang Central Hospital, Yueyang, Hunan, China.
Front Pharmacol. 2025 Jul 8;16:1605531. doi: 10.3389/fphar.2025.1605531. eCollection 2025.
Non-small cell lung cancer (NSCLC) remains a lethal malignancy with limited therapeutic options. Although dihydroartemisinin (DHA) exhibits anticancer properties, its mechanisms in NSCLC are incompletely understood. This study investigated the role of the miR-497-5p/SOX5 axis in mediating DHA's effects on NSCLC.
experiments utilized A549 and H1299 cells treated with DHA (50 μM). Proliferation, migration, invasion, and apoptosis were assessed. miR-497-5p and SOX5 expression was modulated via genetic silencing. , A549 xenograft tumor growth in mice was evaluated under DHA treatment (25/50 mg/kg).
DHA significantly suppressed proliferation, migration, and invasion while inducing apoptosis . Mechanistically, DHA upregulated miR-497-5p and downregulated SOX5-overexpressed in clinical NSCLC. Silencing miR-497-5p attenuated DHA's effects and increased SOX5, whereas SOX5 knockdown reversed miR-497-5p inhibition. , DHA dose-dependently inhibited tumor growth with miR-497-5p elevation and SOX5 suppression, effects abrogated by miR-497-5p inhibition but rescued by SOX5 knockdown.
DHA exerts antitumor activity by activating the miR-497-5p/SOX5 axis, revealing a novel mechanism. Bridging efficacious concentrations with clinically achievable dosing remains essential for therapeutic translation.
非小细胞肺癌（NSCLC）仍然是一种致命的恶性肿瘤，治疗选择有限。虽然双氢青蒿素（DHA）具有抗癌特性，但其在NSCLC中的作用机制尚不完全清楚。本研究调查了miR-497-5p/SOX5轴在介导DHA对NSCLC作用中的作用。
实验使用用DHA（50μM）处理的A549和H1299细胞。评估细胞增殖、迁移、侵袭和凋亡情况。通过基因沉默调节miR-497-5p和SOX5的表达。评估DHA治疗（25/50mg/kg）下小鼠A549异种移植瘤的生长情况。
DHA显著抑制增殖、迁移和侵袭，同时诱导凋亡。机制上，DHA上调临床NSCLC中过表达的miR-497-5p并下调SOX5。沉默miR-497-5p减弱了DHA的作用并增加了SOX5，而敲低SOX5则逆转了miR-497-5p的抑制作用。此外，DHA剂量依赖性地抑制肿瘤生长，同时miR-497-5p升高和SOX5受到抑制，miR-497-5p抑制可消除这些作用，但敲低SOX5可挽救这些作用。
DHA通过激活miR-497-5p/SOX5轴发挥抗肿瘤活性，揭示了一种新机制。将有效浓度与临床可达到的剂量联系起来对于治疗转化仍然至关重要。
